Glucose-Galactose Malabsorption

Synonyms of Glucose-Galactose Malabsorption

Carbohydrate Intolerance of Glucose Galactose

Complex Carbohydrate Intolerance

Monosaccharide Malabsorption

General Discussion

Glucose-galactose malabsorption is an inherited metabolic disorder characterized by the small intestine's inability to transport and absorb glucose and galactose (simple sugars or monosaccharides). Glucose and galactose have very similar chemical structures, and normally the same transport enzyme provides them with entry into specialized cells in the small intestine where they are absorbed and transferred to other cells. As a result of a mutation on chromosome 22, the transport enzyme does not function properly and the result is glucose-galactose malabsorption.

Signs & Symptoms

Symptoms may begin as early as the first day of life or a few days after birth, when the newborn is exposed to lactose from milk. They include severe, chronic diarrhea, dehydration, and failure to thrive. Early recognition and treatment are important. In severe cases, the disorder may become life-threatening.

Among infants, discontinuation of oral feeding may stop the diarrhea but it will start again when oral feeding is reinstated if the child is fed formula containing glucose. The diarrhea can be quite severe and may readily lead to nutritional wasting and severe dehydration.

In some cases, the affected child grows up with chronic but intermittent diarrhea made worse by sugar-rich meals. Modest amounts of sugar in the urine (glucosuria) of an affected child may be a warning that kidney stones are developing.

In adults, symptoms of glucose-galactose malabsorption may include bloating, nausea, diarrhea, abdominal cramps, rumbling sounds caused by gas in the intestine (borborygmi) and excessive urination.

Causes

Glucose-galactose malabsorption (GGM) is inherited as an autosomal recessive trait. The malfunctioning (mutated) gene codes for (initiates the manufacture of) a protein that acts as a transporter of glucose and galactose out of the space enclosed by the small intestine (called the lumen) across the intestinal lining and into intestinal cells.

As a result of a mutation that has been tracked to a gene on the long arm of chromosome 22 (22q13.1), the transporter enzyme cannot do its job properly. There is nowhere for the glucose and galactose to go except into the stools in rather large amounts. Left untransported, these nutrients draw large amounts of water out of the body into the intestinal lumen, leading to an acute diarrhea known as osmotic diarrhea. The gene associated with this disorder is known as SGLT1.

Chromosomes, which are present in the nucleus of human cells, carry the genetic information for each individual. Human body cells normally have 46 chromosomes. Pairs of human chromosomes are numbered from 1 through 22 and the sex chromosomes are designated X and Y. Males have one X and one Y chromosome and females have two X chromosomes. Each chromosome has a short arm designated “p” and a long arm designated “q”. Chromosomes are further sub-divided into many bands that are numbered. For example, “chromosome 22q13.1” refers to band 13.1 on the long arm of chromosome 22. The numbered bands specify the location of the thousands of genes that are present on each chromosome.

Genetic diseases are determined by the combination of genes for a particular trait that are on the chromosomes received from the father and the mother.

Recessive genetic disorders occur when an individual inherits the same abnormal gene for the same trait from each parent. If an individual receives one normal gene and one gene for the disease, the person will be a carrier for the disease, but usually will not show symptoms. The risk for two carrier parents to both pass the defective gene and, therefore, have an affected child is 25% with each pregnancy. The risk to have a child who is a carrier like the parents is 50% with each pregnancy. The chance for a child to receive normal genes from both parents and be genetically normal for that particular trait is 25%. The risk is the same for males and females.

All individuals carry a few abnormal genes. Parents who are close relatives (consanguineous) have a higher chance than unrelated parents to both carry the same abnormal gene, which increases the risk to have children with a recessive genetic disorder.

Affected Populations

Glucose-galactose malabsorption is an extremely rare disorder. It’s been estimated that there are approximately 200 cases worldwide. Two-thirds of those affected are females. One report suggests that about half of the cases of severe GGM reported have occurred among families that have experienced intermarriage (consanguinity).

Related Disorders

Symptoms of the following disorders can be similar to those of glucose- galactose malabsorption. Comparisons may be useful for a differential diagnosis:

Irritable Bowel Syndrome, also called spastic colon, is a disorder involving the muscles of the small intestine, which fail to ingest food at the proper rate. Overly rapid ingestion of food results in diarrhea, and slow ingestion results in constipation. Symptoms include abdominal pain, erratic bowel movements, variation in stool consistency, bloating, flatulence, nausea, headache, fatigue, depression, anxiety and difficulty concentrating. (For more information on this disorder, choose “Irritable Bowel Syndrome” as your search term in the Rare Disease Database.)

Lactose Intolerance is a disorder characterized by a lack of the enzyme lactase which normally breaks down the sugar in milk known as lactose, into simpler sugars. The unabsorbed lactose remains in the intestine, causing symptoms of diarrhea, bloating, cramping pain, nausea and flatulence. People with this disorder must avoid milk and milk products, but can eat other carbohydrates. (For more information on this disorder, choose “Lactose Intolerance” as your search term in the Rare Disease Database.)

Crohn’s Disease is a chronic inflammatory disorder which affects the large intestine. Symptoms may include chronic diarrhea, abdominal pain, fever and weight loss. (For more information on this disorder, choose “Crohn’s Disease” as your search term in the Rare Disease Database.)

Galactosemia is an inherited disorder involving the conversion of galactose to glucose. Symptoms in children may include vomiting, lack of appetite, jaundice and neurological problems. (For more information on this disorder, choose “Galactosemia” as your search term in the Rare Disease Database.)

Diagnosis

The diagnosis is usually made upon review of the presenting signs especially the pervasive, watery diarrhea. A simple test, known as the "glucose breath hydrogen test" is often used to confirm the physical diagnosis.

Standard Therapies

Treatment

Treatment of glucose-galactose malabsorption requires the elimination of all milk and milk products from the diet since milk products contain lactose and lactose is broken down to glucose and galactose. Fructose, a sugar absorbed differently from either glucose or galactose, may be substituted as a source of carbohydrate calories. Most clinicians who treat this disorder recommend the elimination of all lactose, sucrose and glucose from the diet. These sugars may be replaced by fructose-based nutrients.

Investigational Therapies

Information on current clinical trials is posted on the Internet at www.clinicaltrials.gov. All studies receiving U.S. government funding, and some supported by private industry, are posted on this government website.

For information about clinical trials being conducted at the National Institutes of Health (NIH) in Bethesda, MD, contact the NIH Patient Recruitment Office:

Tollfree: (800) 411-1222

TTY: (866) 411-1010

Email: prpl@cc.nih.gov

For information about clinical trials sponsored by private sources, contact:

Years Published

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